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An efficient chiral phosphoric acid catalyzed Biginelli reaction for the synthesis of optically pure 4-alkyl-3,4-dihydropyrimidin-2-(1H)-ones has been developed, with a wide range of the desired products being obtained in moderate to high yields with good to excellent enantioselectivities (up to >99% ee after one recrystallization). The synthetic utility of this reaction is illustrated in various aliphatic bicyclic guanidine compounds, which is applied in the formal synthesis of the bicyclic guanidine core of crambescin A and batzelladine A.

Objective:To evaluate the effects of bisoprolol combined with trimetazidine on the treatment of heart failure patients having concomitant chronic obstructive pulmonary disease (COPD); in comparison with control group treated with standard therapy only.Methods:A total of 120 heart failure patients having concomitant COPD were selected and randomly divided into a control group and a treatment group according to different treatment methods (n=60). The control group was given continuous low flow oxygen inhalation and inotropic agents, and their cardiac stress was also reduced. The treatment group was treated with bisoprolol fumarate and trimetazidine in addition to treatment for COPD. For all patients, blood gas analysis and parameters reflecting cardiac function were measured respectively before and after treatment. The respiratory symptoms (cough, sputum, polypnea, gasp, dyspnea), limitation of motion (daily life, household duties, entertainment, sports), disease impacts (social contact, emotion, anxiety) and St. George’s Respiratory Questionnaire (SGRQ) total scores were observed using SGRQ.Results:The oxygen partial pressure (PaO2) and partial pressure of carbon dioxide (PaCO2) of the treatment group after treatment were significantly different from those before treatment. After treatment, peak E, E/A and IVEF were increased by 41%, 44% and 16% respectively, but peak A, LVPWT/mm and IVST/mm were significantly reduced. The differences in the respiratory symptoms, limitation of motion, disease impacts and SGRQ total scores were statistically significant compared with those before treatment (P<0.05) and those of the control group (P<0.05).Conclusion:Combining bisoprolol with trimetazidine in the treatment of heart failure complicating COPD can effectively improve blood gas indices, left ventricular systolic and diastolic functions and the quality of life, thereby alleviating clinical symptoms.

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